This review focuses on outlining the toxicity of titanium dioxide (TiO2) particulates in vitro and in
vivo, in order to understand their ability to detrimentally impact on human health. Evaluating the
hazards associated with TiO2 particles is vital as it enables risk assessments to be conducted, by
combining this information with knowledge on the likely exposure levels of humans. This review
has concentrated on the toxicity of TiO2, due to the fact that the greatest number of studies by far
have evaluated the toxicity of TiO2, in comparison to other metal oxide particulates. This derives
from historical reasons (whereby the size dependency of particulate toxicity was first realised for
TiO2) and due to its widespread application within consumer products (such as sunscreens). The
pulmonary and dermal hazards of TiO2 have been a particular focus of the available studies, due to
the past use of TiO2 as a (negative) control when assessing the pulmonary toxicity of particulates,
and due to its incorporation within consumer products such as sunscreens. Mechanistic processes
that are critical to TiO2 particulate toxicity will also be discussed and it is apparent that, in the main,
the oxidant driven inflammatory, genotoxic and cytotoxic consequences associated with TiO2
exposure, are inherently linked, and are evident both in vivo and in vitro. The attributes of TiO2 that
have been identified as being most likely to drive the observed toxicity include particle size (and
therefore surface area), crystallinity (and photocatalytic activity), surface chemistry, and particle
aggregation/agglomeration tendency. The experimental set up also influences toxicological
outcomes, so that the species (or model) used, route of exposure, experiment duration, particle
concentration and light conditions are all able to influence the findings of investigations. In addition,
the applicability of the observed findings for particular TiO2 forms, to TiO2 particulates in general,
requires consideration. At this time it is inappropriate to consider the findings for one TiO2 form
as being representative for TiO2 particulates as a whole, due to the vast number of available TiO2
particulate forms and large variety of potential tissue and cell targets that may be affected by
exposure. Thus emphasising that the physicochemical characteristics are fundamental to their
toxicity.